Free energy perturbation study on a Trp-binding mutant (Ser88-->Cys) of the trp-repressor.
Free energy perturbation study on a Trp-binding mutant (Ser88-->Cys) of the trp-repressor.
复制标题
对色氨酸抑制蛋白色氨酸结合突变体 (Ser88-->Cys) 的自由能扰动研究。
DOI：
10.1093/protein/5.8.759
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
I. Yamato
中科院分区：
文献类型：
--
作者：
Y. Komeiji;M. Uebayasi;J. Someya;I. Yamato
trp-阻遏物的Ser 88->Cys突变体显示出比野生型阻遏物更低的对辅阻遏物的亲和力[Δ Δ G = 1.7 +/-0.3 kcal/mol，Chou和马修斯（1989）生物化学杂志，264，18314-18319]。进行分子动力学/自由能循环扰动研究以了解亲和力降低的起源。通过模拟获得了与实验值相当的值（Δ Δ G = 1.58 +/-0.28kcal/mol）。自由能成分分析表明，失稳的货车范德华相互作用之间的Ser 88和Trp 109（辅阻遏物）的主要贡献的突变体的亲和力下降。模拟过程中Ser 88（Cys 88）的羟基（巯基）基团的旋转跃迁影响Arg 84和水对去辅阻遏物中自由能变化的贡献，以及Arg 84和Trp 109对holorepressor中自由能变化的贡献。然而，不同残基的贡献相互补偿，总自由能的变化几乎是不变的各种模拟。
The Ser88-->Cys mutant of the trp-repressor showed a lower affinity for the corepressor than the wild-type repressor [delta delta G = 1.7 +/- 0.3 kcal/mol, Chou and Matthews (1989) J. Biol. Chem., 264, 18314-18319]. A molecular dynamics/free energy cycle perturbation study was performed to understand the origin of the decreased affinity. A value (delta delta G = 1.58 +/- 0.28 kcal/mol) comparable with the experimental value was obtained by the simulation. Free energy component analysis revealed that destabilization of the van der Waals interaction between Ser88 and Trp109 (corepressor) mainly contributed to the decreased affinity of the mutant. The rotational transition of the hydroxyl (sulfhydryl) group of Ser88 (Cys88) during the simulations affected the contributions of Arg84 and water to the free energy change in the aporepressor and those of Arg84 and Trp109 to that in the holorepressor. However, the contributions from different residues compensated each other, and the total free energy changes were almost invariable in the various simulations.